No abstract

Background: Current treatments for depression are limited by suboptimal efficacy, delayed response, and frequent side effects. Intermittent theta-burst stimulation (iTBS) is a non-invasive brain stimulation treatment which is FDA-approved for treatment-resistant depression. Recent studies suggest several improvements could be made to iTBS by 1) precision targeting of the left dorsolateral prefrontal cortex (L-DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit, 2) treating with multiple sessions per day at spaced intervals and 3) applying a higher overall pulse dose of stimulation. Objective: Examine the feasibility, tolerability, and preliminary efficacy of an accelerated, highdose, fcMRI-guided iTBS protocol for treatment-resistant depression (TRD) termed 'Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT)'. Methods: Thirty-one participants with TRD received open-label SAINT. Resting-state functional connectivity MRI (fcMRI) was used to individually target the region of L-DLPFC most anticorrelated with sgACC. Fifty iTBS sessions (1800 pulses per session, 50-minute inter-session interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT. Results: Twenty-eight of 31 participants (90.32%) met criteria for remission (≤10 on the MADRS) and all 31 were remitted on measures of suicidal ideation. Neuropsychological testing demonstrated no negative cognitive side-effects. There were no seizures or other severe adverse events. Discussion: Our highly accelerated, high-dose, iTBS protocol with fcMRI-guided targeting (SAINT) was well tolerated and safe. Efficacy was strikingly high, especially for this treatmentresistant population. Double-blinded sham-controlled trials are required to confirm the high remission rate found in this initial study.

Background: Current treatments for depression are limited by suboptimal efficacy, delayed response, and frequent side effects. Intermittent theta-burst stimulation (iTBS) is a non-invasive brain stimulation treatment that is FDA-approved for treatment-resistant depression (TRD).Recent methodological advancements suggest iTBS could be improved through 1) treating with multiple sessions per day at optimally-spaced intervals, 2) applying a higher overall pulse-dose of stimulation and 3) precision targeting of the left dorsolateral prefrontal cortex (L-DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. We examined the feasibility, tolerability, and preliminary efficacy of an accelerated, high-dose, resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for TRD termed 'Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT)'.Methods: Twenty-one participants with TRD received open-label SAINT. FcMRI was used to individually target the region of L-DLPFC most anticorrelated with sgACC. Fifty iTBS sessions (1800 pulses per session, 50-minute inter-session interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth).Neuropsychological testing was conducted before and after SAINT.Results: Nineteen of 21 participants (90.48%) met criteria for remission (≤10 on the Montgomery-Åsberg Depression Rating Scale) immediately after SAINT. Neuropsychological testing demonstrated no negative cognitive side-effects. There were no seizures or other severe adverse events.Discussion: Our accelerated, high-dose, iTBS protocol with fcMRI-guided targeting (SAINT) was well tolerated and safe. Efficacy was strikingly high, especially for this treatment-resistant population. Double-blinded sham-controlled trials are required to confirm the high remission rate found in this initial study.

Hypnotizability, one’s ability to experience cognitive, emotional, behavioral, and physical changes in response to suggestions in the context of hypnosis, is a highly stable trait associated with increased functional connectivity between the left dorsolateral prefrontal cortex (L-DLPFC) and dorsal anterior cingulate cortex (dACC). We conducted a preregistered, triple-blinded, randomized controlled trial to test the ability of continuous theta-burst stimulation (cTBS) over a personalized neuroimaging-based L-DLPFC target to temporarily enhance hypnotizability. We tested our hypothesis in 78 patients with fibromyalgia syndrome (FMS), a functional pain disorder for which hypnosis has consistently been shown to be beneficial as a nonpharmacological treatment option. Pre-to-post cTBS change in Hypnotic Induction Profile scores (HIP; a standardized measure of hypnotizability) was significantly greater in the Active versus Sham group. Our findings suggest a causal relationship between L-DLPFC and dACC function and hypnotizability. Dose-response optimization should be further examined to formalize guidelines for future clinical utilization.Trial registrationClinicalTrials.govNCT02969707